This phase II, multicentric, national pilot trial is designed to estimate the sustained virological response rate (SVR) following a 12 weeks treatment by telaprevir combined with a 48 or 72 weeks treatment by peginterferon and ribavirin, based upon the rapid virological response (RVR) at week 8 (4 weeks after telaprevir start), and to compare the observed SVR to 20%, a rate determining a significant therapeutic benefit in this population of patients. The primary endpoint will be the SVR defined as undetectable HCV-RNA measured 24 weeks after the end of therapy (EOT).

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:

Estimation of SVR following a 12 wks treatment by telaprevir combined with a 48 or 72 wks peginterferon-ribavirin treatment, based upon the rapid virological response, and comparison to 20% (which would correspond to a significant therapeutic benefit) [ Time Frame: up to 92 weeks or 116 weeks depending on rapid virologic response ] [ Designated as safety issue: No ]

HCV-RNA measured 24 weeks after the end of HCV treatment

Secondary Outcome Measures:

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From week 0 up to 92 weeks or 116 weeks depending on rapid virologic response ] [ Designated as safety issue: Yes ]

Estimation of the Sustained Virological Response defined as undetectable HCV-RNA at Week 12 after the end of HCV treatment [ Time Frame: at Week 60 or Week 84 depending on rapid virologic response ] [ Designated as safety issue: No ]

And stable antiretroviral treatment for over 3 months among the authorized combinations: (tenofovir 300 mg, emtricitabine 200 mg, atazanavir 300 mg, ritonavir 100 mg) q.d. or (tenofovir 300 mg, emtricitabine 200 mg, efavirenz 600 mg) q.d. or (tenofovir 300 mg, emtricitabine 200 mg q.d. and raltegravir 400 mg b.i.d.) once Drug-Drug interaction data will be available. Patients who could not receive one of these 3 combinations can be included if they are receiving a stable combination of at least 3 drugs among the following: tenofovir, emtricitabine/lamivudine, efavirenz, atazanavir-boosted or not, raltegravir (once Drug-Drug interaction data will be available). These patients cannot participate in the pharmacokinetic study.

The trial will enroll 80 subjects. The proportion of patients included, presenting with cirrhosis (METAVIR F4) will remain below 50% of all patients The proportion of patients included, null-responders to previous HCV treatment (HCV-RNA decline at week 12 less than 2 log10 UI/ml) but no cirrhosis (maximum equal METAVIR F3) will remain below 30% of patients.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Informed consent form signed at screening visit at the latest

Patient registered with or covered by a social security scheme

HIV-1 infection

Chronic, genotype 1, hepatitis C with detectable HCV RNA at screening

Virological failure following a previous treatment of at least 12 weeks by peginterferon alpha-2a ≥ 135 µg once weekly or peginterferon alpha-2b ≥ 1.0 µg per kg once weekly + ribavirin ≥ 600 mg once daily. Virological failure defined by persistence of a detectable HCV-RNA, with the same genotype than before. Null responder patient, with less than 2 Log10 HCV-RNA decline at week 12 with cirrhosis are excluded from the study. Null responder patients without cirrhosis (equal or below METAVIR F3) are limited to less than 30 % of all patients included

No Interferon and/or Ribavirin within past 6 months

Stable antiretroviral treatment for over 3 months at screening. Authorized combinations: tenofovir-emtricitabine-boosted atazanavir,tenofovir-emtricitabine-efavirenz,tenofovir-emtricitabine-raltegravir, once Drug-Drug interaction data will be available. Patients with a stable combination of at least 3 of the following drugs: tenofovir, emtricitabine/lamivudine, efavirenz, atazanavir-boosted or not, raltegravir. These patients cannot participate in the pharmacokinetic study

CD4 >200/mm3 and >15% at screening

Plasma HIV-RNA <50 copies/mL for at least 6 months at screening visit

Body weight ≥ 40 kg to equal or below 125 kg

Fibrosis stage have to be documented by a significant liver biopsy (cumulative length ≥ 15 mm or ≥ 6 portal spaces), within 3 years. Patients with a previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4) are allowed to enter the study without a new biopsy. The proportion of patients with cirrhosis lesions (METAVIR F4) is limited to 50% of all patients.

Male patients, female patients with child-bearing potency and their heterosexual partners must use an adequate contraception from 1 month before initiation of treatment to 7 months following the end of treatment for men and to 4 months following the end of treatment for women. Subjects (or their female partners) must not be pregnant or planning to become pregnant within 2 years after enrolling in the study

Exclusion Criteria:

Patient with liver failure (Child B and C) or past history of decompensated cirrhosis

Significant oesophageal varices (Stages 2-3) on a gastrointestinal endoscopy within 3 years

Detectable AgHBs

HIV-2 co-infection

Contra-indication to ribavirin or peginterferon

Severe pre-existing cardiac or pulmonary disease

Untreated dysthyroidism

Uncontrolled Type 2 diabetes

Optic neuritis past history and retinal condition

History of organ transplant

Severe hemoglobinopathy

Congenital QT prolongation, family history of congenital QT prolongation or sudden unexpected death

Contra-indication to telaprevir, hypersensitivity to any component of the drug product

Any disease requiring long term, systemic corticotherapy or immunosuppressive therapy during study

Alcohol intake that may represent an obstacle for the participation of the subject

Substance abuse that may represent an obstacle for the participation of the subject

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332955